Nomenclature of Absolute Configuration: (R,S) System - Sequencing Rules
The D,L system, proposed by M. A. Rosanoff in 1906, is still used for naming amino acids and carbohydrates but it is not unequivocal in all cases and cannot easily be applied to all families of compounds. Therefore, an unequivocal and generally applicable nomenclature is necessary to distinguish between stereoisomers, differing only in their absolute configuration. For instance, the simplest chiral alcohol, 2-butanol, forms two different enantiomers, which are not distinguishable by the name 2-butanol.
In the early sixties, R. S. Cahn (England), C. K. Ingold (England), and V. Prelog (Switzerland) introduced the unequivocal and generally applicable (R,S) system (also called Cahn-Ingold-Prelog or CIP system) for naming the absolute configuration of chirality centers. Modified (R,S) systems can also be applied to chirality axes and planes. The CIP sequencing rules are the basis of the (R,S) system.
CIP sequencing rules
|Rule 1 According to the CIP sequencing rules, the four substituents of a tetrahedral chirality center are ranked in order of decreasing atomic number of the atoms directly bonded to the chirality center. Isotopes of the same chemical element are listed in order of decreasing atomic mass.|
|Rule 2 Where two or more atoms bonded to the chirality center have the same atomic number, the second atoms are used to rank the substituents. If the second atoms are also the same, the third are used, and so on. In the illustration, this is explained by different distance spheres around the chirality center of 2-butanol. Atoms directly bonded to the asymmetric carbon are inside the innermost square and so on. In this case, the CIP sequence of the atoms directly bonded to the chirality center C2 is: O > C1 = C3 > H. According to the first rule, carbon atoms C1 and C3 cannot be distinguished. In the second sphere, C1 is connected to three hydrogens, while C3 is connected to two hydrogens and one carbon. Therefore, C3 precedes C1 and the final CIP sequence is: O > C3 > C1 > H.|
|Rule 3 Multiple bonds are counted as the corresponding number of single bonds. A double-bonded atom is counted twice, a triple-bonded atom three times, and so on. For instance, according to the CIP rules the carbon of a keto group is equated with a carbon carrying two single-bonded oxygens.|